Vaccine World MENA & CIS 2014, Istanbul Quality-by-Design (QbD) in Vaccine development

Transcription

1 Vaccine World MENA & CIS 2014, Istanbul -by- (QbD) in Vaccine developm Presed by: Dr. Reinhard Glueck Chief Sciific Officer Vaccine Technology Cer, Cadila Healthcare Ltd., India

2 Zydus Cadila, Vaccine Technology Cer 2

3 Zydus Cadila, Vaccine Technology Cer 3

4 Why QbD? can not be tested into products; it has to be built in by design Page 4

5 How QbD will help? More knowledge of our products and processes, allowing better design and more Better managem: - introduction of quality risk managem - expansion of GMP to more extensive pharmaceutical quality system Page 5

6 What is QbD? A systematic approach to developm, that begins with predefined objectives, and emphasizes - product and process understanding - and process, based on sound science and quality risk managem. Page 6

7 life cycle Process Scale-up & Transfer Commercial Manufacture ICH Q8/Q8(R) - Pharmaceutical Developm PAT Guidance ICH Q9 Risk ICH Q10 Pharmaceutical Systems Page 7

8 Establishm of QbD Step 1. Create Step 2. Determine the Step 3. Link the product attributes and the process parameters (CPPs) to the CQAs Step 4. the Step 5. the Control Strategy Step 6. lifecycle managem and continual process improvem Page 8

9 Key Elems QUALITY BY DESIGN Page 9

10 Step 1: Create (QTPP) target product profile is a prospective and dynamic summary of the quality characteristics of a drug product that ideally will be achieved to ensure that the desired safety, idity, strength, purity and quality of a vaccine is achieved. Points to be considered are: age group and population (Infants, Adults) Route of administration (Oral, I/M, S/C) Storage conditions and target shelf-life Dosage form (Liquid/Lyophilized) Strength required for immunity Page 10

11 Step 2: Determine quality attribute is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. These attributes are responsible for product purity, efficacy, stability and ultimately release. Examples include: Sterility Bacterial endotoxins Potency Page 11

12 Step 3: Linking of the critical process parameters (CPPs) to the CQAs INPUT (CRITICAL PROCESS PARAMETERS) MAN (Employees) MACHINE (Equipms) OUTPUT (CRITICAL QUALITY ATTRIBUTES) MATERIAL (RM, PM) MEASUREMENT (QC) METHOD (ion) QUALITY PRODUCT MILEAU (Environm) Page 12

13 Step 3: Linking of the critical process parameters (CPPs) to the CQAs of experims (DOE) is carried out to determine relations between CPPs and CQAs Selection of experimal designs Execution of randomized experims to idify criticality of process parameters (using Statistical tools) Data analysis to correlate impact of critical process parameters over CQAs. Page 13

14 Step 3: Linking of the critical process parameters (CPPs) to the CQAs Inputs (CPPs) Outputs Stirrer RPM ph Pressure OD Cycle duration Purity RM feeding Page 14

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16 Step 4: the space is multidimensional combination and interaction of input variables (e.g. material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movem out of the design space is considered to be a change and would initiate a regulatory post approval change process. Page 16

17 Roller RPM Step 4: the % Cell Death space % Infection Page 17

18 Step 4: the Knowledge space space Control space % Infection Page 18

19 Step 5: the Control Strategy The strategy should describe and justify how. s of input materials (drug substance and excipis, container closure system, in-process s intermediates and the s of end products. contribute to the final product quality Page 19

20 Step 5: the Control Strategy Controls of input materials includes - Vendor approvals QC released raw materials Highly purified input materials Approved drug substance and excipis Compatible container closure system, Selection of materials shall be based on an understanding of their impact on process suitability and product quality. Page 20

21 Step 5: the Control Strategy Inprocess s are - Control on unit operations that may have direct or indirect impact on product quality Implemation of Good manufacturing practices specifications In-process releases in lieu of end product testing Area, equipm and process monitoring program for verification of process variability Page 21

22 Step 6: lifecycle managem and continual process improvem Minimal approach is reactive and performs corrective actions against failures Not suitable approach is proactive and involves previve actions to build quality into product. Each process improvem is verified against results of of Experims (DOE) so that the impact is minimized over the product quality. Page 22

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24 is never an accid. It is always the result of high intion, sincere efforts and intellig direction and skillful execution. 24

25 Thank you!!! 25